The Role of Polymorphonuclear Leucocytes in the Pulmonary Dysfunction Induced by Complement Activation

Abstract

To determine the role of polymorphonuclear leukocytes (PMN) in the pulmonary reaction induced by complement activation, pigs were infused with complement-activated plasma (CAP), cell-free supernatant from PMN activated in vitro, or washed PMN aggregates produced in vitro. Infusion of CAP resulted in transient peripheral leukopenia, a reversible rise in pulmonary vascular resistance (PVR) and decreased arterial oxygen tension (PaO2). Indomethacin did not influence the CAP-induced drop in PMN count or the accumulation of PMN in the lung, but significantly counteracted the rise in PVR and fall in PaO2. Antihistamines did not prevent the cellular or pulmonary reactions to CAP infusion. Methylprednisolone did not inhibit the decrease in PMN count, but modified the pulmonary reaction to CAP, although it did not prevent the rise in PVR to the same extent as indomethacin; it counteracted the fall in PaO2. Infusion of supernatant from activated PMN did not influence the PMN count, but caused a reversible increase in PVR and a drop in PaO2. Indomethacin counteracted the pulmonary reaction to this infusion. Infusion of washed PMN aggregates did not result in any cellular or physiological changes. The pulmonary reaction induced by complement activation is mediated by humoral components generated and/or released during activation of PMN. Arachidonic acid metabolites play an important role and it is likely that substance(s) released from activated PMN trigger prostanoid synthesis in other cells. PMN exposed to activated complement factors also directly synthesize and release arachidonic acid metabolites.